Fetal Alcohol Syndrome (FAS) is a devastating condition that affects numerous children. Important steps in designing treatments for FAS are to understand the mechanisms of alcohol-induced neuronal cell death, as well as cellular pathways that may protect against this neurotoxicity. The nitric oxide - cyclic GMP - cyclic GMP-dependent protein kinase (NO-cGMP-PKG) pathway, which is activated by neurotrophic factors such as NMDA and NGF, is protective against alcohol-induced cell death in vitro. The disruption of the neuronal nitric oxide synthase gene in mice (nNOS-/-) enhances the vulnerability of developing cerebellar neurons to alcohol-induced toxicity in vivo. This project will determine whether this increased vulnerability to alcohol in nNOS-/- mice correlates with a functional deficit on cerebellar-dependent behavioral tasks, including locomotor activity, balance, gait and classical eyeblink conditioning. These behavioral deficits may be correlated with cerebellar cell numbers. An unbiased stereological technique will be used to count the number of granule, Purkinje and deep cerebellar nuclei cells. This project may thereby further support the hypothesis that the NO-cGMP-PKG pathway is protective against alcohol-induced toxicity and the associated motor impairments, which are also observed in FAS children.